Premature senescence in human melanocytes after exposure to solar UVR: An exosome and UV-miRNA connection.

Ultraviolet radiation (UVR) can play two roles: induce cellular senescence and convert skin melanocytes into melanoma. To assess whether this conversion might rely on melanocytes having to first acquire a senescent phenotype, we studied the effects of physiological doses of UVR (UVA + UVB) on quiescent melanocytes in vitro. Repeated doses of UVR induced these melanocytes into a senescent-like state. Additionally, these cells secrete exosomes with specific miRNAs that differ in quantity from those of the un-irradiated melanocytes. Many of the exosomal miRNAs that were differentially enriched regulated genes comprising a "senescence core signature" and encoding factors of the senescence-messaging secretome (SASP), while a subset of the differentially reduced miRNAs targeted DNA repair genes that have been experimentally shown to be repressed in senescent melanocytes. Thus, the selection of specific miRNAs by exosomes and their release from melanocytes after exposure to UVR have activities in inducing these cells into premature senescence.